Department of Stem Cell and Regenerative Biology, Department of Molecular and Cellular Biology, Harvard Stem Cell Institute, Cambridge, MA, 02138, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Mol Autism. 2021 Feb 8;12(1):10. doi: 10.1186/s13229-021-00417-x.
Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by impaired social interactions as well as the presentation of restrictive and repetitive behaviors. ASD is highly heritable but genetically heterogenous with both common and rare genetic variants collaborating to predispose individuals to the disorder. In this review, we synthesize recent efforts to develop human induced pluripotent stem cell (iPSC)-derived models of ASD-related phenotypes. We firstly address concerns regarding the relevance and validity of available neuronal iPSC-derived models. We then critically evaluate the robustness of various differentiation and cell culture protocols used for producing cell types of relevance to ASD. By exploring iPSC models of ASD reported thus far, we examine to what extent cellular and neuronal phenotypes with potential relevance to ASD can be linked to genetic variants found to underlie it. Lastly, we outline promising strategies by which iPSC technology can both enhance the power of genetic studies to identify ASD risk factors and nominate pathways that are disrupted across groups of ASD patients that might serve as common points for therapeutic intervention.
自闭症谱系障碍（ASD）是一组神经发育障碍，其特征是社交互动受损以及表现出限制和重复的行为。ASD 具有高度遗传性，但遗传异质性，常见和罕见的遗传变异共同导致个体易患该疾病。在这篇综述中，我们综合了最近开发与 ASD 相关表型的人类诱导多能干细胞（iPSC）衍生模型的努力。我们首先解决了对现有神经元 iPSC 衍生模型相关性和有效性的担忧。然后，我们批判性地评估了用于产生与 ASD 相关的细胞类型的各种分化和细胞培养方案的稳健性。通过探索迄今为止报道的 ASD 的 iPSC 模型，我们研究了与 ASD 相关的潜在相关细胞和神经元表型在多大程度上可以与潜在 ASD 的遗传变异联系起来。最后，我们概述了 iPSC 技术增强遗传研究识别 ASD 风险因素的能力并提名跨 ASD 患者群体被破坏的途径的有前途的策略，这些途径可能成为治疗干预的共同点。
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